Search results for: evolutionary marker

Authors: M. M. Rahman, A. Liu, A. Frostegard, J. Frostegard

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The human immune system plays an essential role in cardiovascular disease (CVD) and atherosclerosis. Our earlier studies showed that major immunocompetent cells including T cells are activated by phosphorylcholine epitope. Further, we have determined for the first time in a clinical cohort that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with the development of atherosclerosis and thus a low risk of cardiovascular diseases. It is still unknown whether activated T cells play a role in anti-PC production. Here we aim to clarify the role of T cells in anti-PC production. B cell alone, or with CD3 T, CD4 T or with CD8 T cells were cultured in polystyrene plates to examine anti-PC IgM production. In addition to mixed B cell with CD3 T cell culture, B cells with CD3 T cells were also cultured in transwell co-culture plates. Further, B cells alone and mixed B cell with CD3 T cell cultures with or without anti-HLA 2 antibody were cultured for 6 days. Anti-PC IgM was detected by ELISA in independent experiments. More than 8 fold higher levels of anti-PC IgM were detected by ELISA in mixed B cell with CD3 T cell cultures in comparison to B cells alone. After the co-culture of B and CD3 T cells in transwell plates, there were no increased antibody levels indicating that B and T cells need to interact to augment anti-PC IgM production. Furthermore, anti-PC IgM was abolished by anti-HLA 2 blocking antibody in mixed B and CD3 T cells culture. In addition, the lack of increased anti-PC IgM in mixed B with CD8 T cells culture and the increased levels of anti-PC in mixed B with CD4 T cells culture support the role of helper T cell for the anti-PC IgM production. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC IgM is a protection marker for atherosclerosis development. Understanding the mechanism involved in the anti-PC IgM regulation could play an important role in strategies to raise anti-PC IgM. Studies suggest that anti-PC is T-cell independent antibody, but our study shows the major role of T cell in anti-PC IgM production. Activation of helper T cells by immunization could be a possible mechanism for raising anti-PC levels.

Keywords: anti-PC, atherosclerosis, aardiovascular diseases, phosphorylcholine

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Authors: Mohammed Jarrar, Shalini Behl, Nadia Shaheen, Abeer Fatima, Reem Nasab

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Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is crucial on aging of skin by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photo-damage is highly valued. Retinoids and Alpha Hydroxy Acids protective and or repairing effects of UV have been endorsed by some researchers. For consolidating a better understanding of anti and protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblasts elastin levels exposed to UV. The UV exposed cells showed significant reduction in the elastin levels. A combination of drugs with a higher concentration of lactic acid (30-35 mM) and a lower concentration of retinol (10-15mg/mL) showed to work better in enhancing elastin concentration in UV exposed cells. We assume this enhancement could be the result of increased tropo-elastin gene expression stimulated by retinol and lactic acid probably repaired the UV irradiated damage by enhancing the amount and integrity of the elastin fibers.

Keywords: alpha hydroxy acid, elastin, retinol, ultraviolet radiations

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Authors: Hamide Farshad, Mohammadreza Javidi Abdollah Zadeh Aval

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As a result of the growing penetration of the media into human life, a new role under the title of "audience" is defined in the social life .A kind of role which is dramatically changed since its formation. This article aims to define the audience position in the new media equations which is concluded to the transformation of the media role. By using the Library and Attributive method to study the history, the evolutionary outlook to the audience and the recognition of the audience and the media relation in the new media context is studied. It was perceived in past that public communication would result in receiving the audience. But after the emergence of the interactional media and transformation in the audience social life, a new kind of public communication is formed, and also the imaginary picture of the audience is replaced by the audience impact on the communication process. Part of this impact can be seen in the form of feedback which is one of the public communication elements. In public communication, the audience feedback is completely accepted. But in many cases, and along with the audience feedback, the media changes its direction; this direction shift is known as media feedback. At this state, the media and the audience are both doers and consistently change their positions in an interaction. With the greater number of the audience and the media, this process has taken a new role, and the role of this doer is sometimes taken by an audience while influencing another audience, or a media while influencing another media. In this article, this multiple public communication process is shown through representing a model under the title of ”The bilateral influence of the audience and the media.” Based on this model, the audience and the media power are not the two sides of a coin, and as a result, by accepting these two as the doers, the bilateral power of the audience and the media will be complementary to each other. Also more, the compatibility between the media and the audience is analyzed in the bilateral and interactional relation hypothesis, and by analyzing the action law hypothesis, the dos and don’ts of this role are defined, and media is obliged to know and accept them in order to be able to survive. They also have a determining role in the strategic studies of a media.

Keywords: audience, effect, media, interaction, action laws

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Authors: N. G. Vepkhvadze, T. Enukidze

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Anthrax is a fatal disease caused by strains of Bacillus anthracis, a spore-forming gram-positive bacillus that causes the disease anthrax in animals and humans. Anthrax is a zoonotic disease that is also well-recognized as a potential agent of bioterrorism. Infection in humans is extremely rare in the developed world and is generally due to contact with infected animals or contaminated animal products. Testing of this zoonotic disease began in 1907 in Georgia and is still being tested routinely to provide accurate information and efficient testing results at the State Laboratory of Agriculture of Georgia. Each clinical sample is analyzed by RT-PCR and bacteriology methods; this study used Real-Time PCR assays for the detection of B. anthracis that rely on plasmid-encoded targets with a chromosomal marker to correctly differentiate pathogenic strains from non-anthracis Bacillus species. During the period of 2015-2022, the State Laboratory of Agriculture (SLA) tested 250 clinical and environmental (soil) samples from several different regions in Georgia. In total, 61 out of the 250 samples were positive during this period. Based on the results, Anthrax cases are mostly present in Eastern Georgia, with a high density of the population of livestock, specifically in the regions of Kakheti and Kvemo Kartli. All laboratory activities are being performed in accordance with International Quality standards, adhering to biosafety and biosecurity rules by qualified and experienced personnel handling pathogenic agents. Laboratory testing plays the largest role in diagnosing animals with anthrax, which helps pertinent institutions to quickly confirm a diagnosis of anthrax and evaluate the epidemiological situation that generates important data for further responses.

Keywords: animal disease, baccilus anthracis, edp, laboratory molecular diagnostics

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Authors: Sara Ataei, Maryam Taghizadeh-Ghehi, Amir Sarayani, Asieh Ashouri, Amirhossein Moslehi, Molouk Hadjibabaie, Kheirollah Gholami

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Background: Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation (HSCT) patients with an incidence of 21–73%. Prevention and early diagnosis reduces the frequency and severity of this complication. Predictive biomarkers are of major importance to timely diagnosis. Neutrophil gelatinase associated lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. Methods: We performed further analyses on gathered data from our recent trial to evaluate the performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT patients. AKI diagnosis and severity were assessed using Risk–Injury–Failure–Loss–End-stage renal disease and AKI Network criteria. We assessed uNGAL on days -6, -3, +3, +9 and +15. Results: Time-dependent Cox regression analysis revealed a statistically significant relationship between uNGAL and AKI occurrence. (HR=1.04 (1.008-1.07), P=0.01). There was a relation between uNGAL day +9 to baseline ratio and incidence of AKI (unadjusted HR=.1.047(1.012-1.083), P<0.01). The area under the receiver-operating characteristic curve for day +9 to baseline ratio was 0.86 (0.74-0.99, P<0.01) and a cut-off value of 2.62 was 85% sensitive and 83% specific in predicting AKI. Conclusions: Our results indicated that increase in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations from baseline could be of value for predicting AKI in HSCT patients. Additionally uNGAL changes preceded serum creatinine rises by nearly 2 days.

Keywords: acute kidney injury, hemtopoietic stem cell transplantation, neutrophil gelatinase-associated lipocalin, Receiver-operating characteristic curve

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Authors: Techale B., Hongxu Dong, Mihrete Getinet, Aregash Gabizew, Andrew H. Paterson, Kassahun Bantte

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The genetic architecture of drought tolerance is expected to involve multiple loci that are unlikely to all segregate for alternative alleles in a single bi-parental population. Therefore, the identification of quantitative trait loci (QTL) that are expressed in diverse genetic backgrounds of multiple bi-parental populations provides evidence about both background-specific and common genetic variants. The purpose of this study was to map QTL related to drought tolerance using three connected mapping populations of different genetic backgrounds to gain insight into the genomic landscape of this important trait in elite Ethiopian germplasm. The three bi-parental populations, each with 207 F₂:₃ lines, were evaluated using an alpha lattice design with two replications under two moisture stress environments. Drought tolerance related traits were analyzed separately for each population using composite interval mapping, finding a total of 105 QTLs. All the QTLs identified from individual populations were projected on a combined consensus map, comprising a total of 25 meta QTLs for seven traits. The consensus map allowed us to deduce locations of a larger number of markers than possible in any individual map, providing a reference for genetic studies in different genetic backgrounds. The mQTL identified in this study could be used for marker-assisted breeding programs in sorghum after validation. Only one trait, reduced leaf senescence, showed a striking bias of allele distribution, indicating substantial standing variation among present varieties that might be employed in improving drought tolerance of Ethiopian and other sorghums.

Keywords: Drought tolerance , Mapping populations, Meta QTL, QTL mapping, Sorghum

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Authors: J. E. O. Hernandez

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In the next 20 years, energy production by burning fuels will increase and so will the atmospheric concentration of CO2 and its well-known threats to life on Earth. The technologies available for capturing CO2 are still dubious and this keeps fostering an interest in bio-inspired approaches. The leading one is the application of carbonic anhydrase (CA) –a superfast biocatalyst able to convert up to one million molecules of CO2 into carbonates in water. However, natural CA underperforms when applied to real smoky CO2 in chimneys and, so far, the efforts to create superior CAs in the lab rely on screening methods running under pristine conditions at the micro level, which are far from resembling those in chimneys. For the evolution of man-made enzymes, selection rather than screening would be ideal but this is challenging because of the need for a suitable artificial environment that is also sustainable for our society. Herein we present the stepwise design and construction of a bioprocess (from bench-scale to semi-pilot) for evolutionary selection experiments. In this bioprocess, reaction and adsorption took place simultaneously at atmospheric pressure in a spray tower. The scrubbing solution was fed countercurrently by reusing municipal pressure and it was mainly prepared with water, carbonic anhydrase and calcium chloride. This bioprocess allowed for the enzymatic carbonation of smoky CO2; the reuse of process water and the recovery of solid carbonates without cooling of smoke, pretreatments, solvent amines and compression of CO2. The average yield of solid carbonates was 0.54 g min-1 or 12-fold the amount produced in serum bottles at lab bench scale. This bioprocess could be used as a tailor-made environment for driving the selection of superior CAs. The bioprocess and its match CA could be sustainably used to reduce global warming by CO2 emissions from exhausts.

Keywords: biological carbon capture and sequestration, carbonic anhydrase, directed evolution, global warming

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Authors: Tanveer Hussain, Misbah Hussain, Masroor Ellahi Babar, Muhammad Traiq Pervez, Fiaz Hussain, Sana Zahoor, Rashid Saif

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Interleukin 2 (IL-2) is a cytokine which is produced by activated T cells, play important role in immune response against antigen. It act in both autocrine and paracrine manner. It can stimulate B cells and various other phagocytic cells like monocytes, lymphokine-activated killer cells and natural killer cells. Acting in autocrine fashion, IL-2 protein plays a crucial role in proliferation of T cells. IL-2 triggers the release of pro and anti- inflammatory cytokines by activating several pathways. In present study, exon 1 of IL-2 gene of four local Pakistani breeds (Dera Din Panah, Beetal, Nachi and Kamori) from two provinces was amplified by using reported Ovine IL-2 primers, yielding PCR product of 501 bp. The sequencing of all samples was done to identify the polymorphisms in amplified region of IL-2 gene. Analysis of sequencing data resulted in identification of one novel nucleotide substitution (T→A) in amplified non-coding region of IL-2 gene. Comparison of IL-2 gene sequence of all four breeds with other goat breeds showed high similarity in sequence. While phylogenetic analysis of our local breeds with other mammals showed that IL-2 is a variable gene which has undergone many substitutions. This high substitution rate can be due to the decreased or increased changed selective pressure. These rapid changes can also lead to the change in function of immune system. This pioneering study of Pakistani goat breeds urge for further studies on immune system of each targeted breed for fully understanding the functional role of IL-2 in goat immunity.

Keywords: interleukin 2, mutational analysis, phylogeny, goat breeds, Pakistan

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Authors: Luis C. Parra

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The significant wave height prediction is an issue of great interest in the field of coastal activities because of the non-linear behavior of the wave height and its complexity of prediction. This study aims to present a machine learning model to forecast the significant wave height of the oceanographic wave measuring buoys anchored at Mooloolaba of the Queensland Government Data. Modeling was performed by a multilayer perceptron neural network-genetic algorithm (GA-MLP), considering Relu(x) as the activation function of the MLPNN. The GA is in charge of optimized the MLPNN hyperparameters (learning rate, hidden layers, neurons, and activation functions) and wrapper feature selection for the window width size. Results are assessed using Mean Square Error (MSE), Root Mean Square Error (RMSE), and Mean Absolute Error (MAE). The GAMLPNN algorithm was performed with a population size of thirty individuals for eight generations for the prediction optimization of 5 steps forward, obtaining a performance evaluation of 0.00104 MSE, 0.03222 RMSE, 0.02338 MAE, and 0.71163% of MAPE. The results of the analysis suggest that the MLPNNGA model is effective in predicting significant wave height in a one-step forecast with distant time windows, presenting 0.00014 MSE, 0.01180 RMSE, 0.00912 MAE, and 0.52500% of MAPE with 0.99940 of correlation factor. The GA-MLP algorithm was compared with the ARIMA forecasting model, presenting better performance criteria in all performance criteria, validating the potential of this algorithm.

Keywords: significant wave height, machine learning optimization, multilayer perceptron neural networks, evolutionary algorithms

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Authors: T. Abdulkadir

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Most often, marking and assessment of multiple choice kinds of examinations have been opined by many as a cumbersome and herculean task to accomplished manually in Nigeria. Usually this may be in obvious nexus to the fact that mass numbers of candidates were known to take the same examination simultaneously. Eventually, marking such a mammoth number of booklets dared and dread even the fastest paid examiners who often undertake the job with the resulting consequences of stress and boredom. This paper explores the evolution, as well as the set aim to envision and transcend marking the Multiple Choice Objectives- type examination into a thing of creative recreation, or perhaps a more relaxing activity via the use of the mobile phone. A more “pragmatic” dimension method was employed to achieve this work, rather than the formal “in-depth research” based approach due to the “novelty” of the mobile-smartphone e-Marking Scheme discovery. Moreover, being an evolutionary scheme, no recent academic work shares a direct same topic concept with the ‘use of cell phone as an e-marking technique’ was found online; thus, the dearth of even miscellaneous citations in this work. Additional future advancements are what steered the anticipatory motive of this paper which laid the fundamental proposition. However, the paper introduces for the first time the concept of mobile-smart phone e-marking, the steps to achieve it, as well as the merits and demerits of the technique all spelt out in the subsequent pages.

Keywords: cell phone, e-marking scheme (eMS), mobile phone, mobile-smart phone, multiple choice objectives (MCO), smartphone

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Authors: Dake Xiong, Ben Hankamer, Ian Ross

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The most urgent challenge of our time is to replace the depleting resources of fossil fuels by sustainable environmentally friendly alternatives. Hydrogen is a promising CO2-neutral fuel for a more sustainable future especially when produced photo-biologically. Hydrogen can be photosynthetically produced in unicellular green alga like Chlamydomonas reinhardtii, catalysed by the inducible highly active and bidirectional [FeFe]-hydrogenase enzymes (HydA). However, evolutionary and physiological constraints severely restrict the hydrogen yield of algae for industrial scale-up, mainly due to its competition among other metabolic pathways on photosynthetic electrons. Among them, a major challenge to be resolved is the inferior competitiveness of hydrogen production (catalysed by HydA) with NADPH production (catalysed by ferredoxin-NADP+-reductase (FNR)), which is essential for cell growth and takes up ~95% of photosynthetic electrons. In this work, the in vivo hydrogen production efficiency of mutants with ferredoxin-hydrogenase (Fd*-HydA1*) fusion protein construct, where the electron donor ferredoxin (Fd*) is fused to HydA1* and expressed in the model organism C. reinhardtii was investigated. Once Fd*-HydA1* fusion gene is expressed in algal cells, the fusion enzyme is able to draw the redistributed photosynthetic electrons and use them for efficient hydrogen production. From preliminary data, mutants with Fd*-HydA1* transgene showed a ~2-fold increase in the photosynthetic hydrogen production rate compared with its parental strain, which only possesses the native HydA in vivo. Therefore, a solid method of having more efficient hydrogen production in microalgae can be achieved through the expression of the synthetic enzymes.

Keywords: Chlamydomonas reinhardtii, ferredoxin, fusion protein, hydrogen production, hydrogenase

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Authors: Ali Algryani

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Ellipsis involves the omission of an item or items that can be recovered from the preceding clause. Ellipsis is used as a cohesion marker; it enhances the cohesiveness of a text/discourse as a clause is interpretable only through making reference to an antecedent clause. The present study attempts to investigate the linguistic phenomenon of ellipsis from a translation perspective. It is mainly concerned with how ellipsis is translated from English into Arabic. The study covers different forms of ellipsis, such as noun phrase ellipsis, verb phrase ellipsis, gapping, pseudo-gapping, stripping, and sluicing. The primary aim of the study, apart from discussing the use and function of ellipsis, is to find out how such ellipsis phenomena are dealt with in English-Arabic translation and determine the implications of the translations of elliptical structures into Arabic. The study is based on the analysis of Dhofar University (DU) students' translations of sentences containing different forms of ellipsis. The initial findings of the study indicate that due to differences in syntactic structures and stylistic preferences between English and Arabic, Arabic tends to use lexical repetition in the translation of some elliptical structures, thus achieving a higher level of explicitness. This implies that Arabic tends to prefer lexical repetition to create cohesion more than English does. Furthermore, the study also reveals that the improper translation of ellipsis leads to interpretations different from those understood from the source text. Such mistranslations can be attributed to student translators’ lack of awareness of the use and function of ellipsis as well as the stylistic preferences of both languages. This has pedagogical implications on the teaching and training of translation students at DU. Students' linguistic competence needs to be enhanced through teaching linguistics-related issues with reference to translation and both languages, .i.e. source and target languages and with special emphasis on their use, function and stylistic preferences.

Keywords: cohesion, ellipsis, explicitness, lexical repetition

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Authors: Thilini Hathurusinghe, Uthpalie Siriwardhana, W. M. Ediri Arachchi, Ranga Thudugala, Indeewari Herath, Gayani Senanayake

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The foramen magnum is more prone to protect than other skeletal remains during high impact and severe disruptive injuries. Therefore, it is worthwhile to explore whether these measurements can be used to determine the human gender which is vital in forensic and anthropological studies. The idea was to find out the ability to use quantitative measurements of foramen magnum as an anatomical indicator for human gender estimation and to evaluate the gender-dependent variations of foramen magnum using quantitative measurements. Randomly selected 113 subjects who underwent CT head scans at Sri Jayawardhanapura General Hospital of Sri Lanka within a period of six months, were included in the study. The sample contained 58 males (48.76 ± 14.7 years old) and 55 females (47.04 ±15.9 years old). Maximum length of the foramen magnum (LFM), maximum width of the foramen magnum (WFM), minimum distance between occipital condyles (MnD) and maximum interior distance between occipital condyles (MxID) were measured. Further, AreaT and AreaR were also calculated. The gender was estimated using binomial logistic regression. The mean values of all explanatory variables (LFM, WFM, MnD, MxID, AreaT, and AreaR) were greater among male than female. All explanatory variables except MnD (p=0.669) were statistically significant (p < 0.05). Significant bivariate correlations were demonstrated by AreaT and AreaR with the explanatory variables. The results evidenced that WFM and MxID were the best measurements in predicting gender according to binomial logistic regression. The estimated model was: log (p/1-p) =10.391-0.136×MxID-0.231×WFM, where p is the probability of being a female. The classification accuracy given by the above model was 65.5%. The quantitative measurements of foramen magnum can be used as a reliable anatomical marker for human gender estimation in the Sri Lankan context.

Keywords: foramen magnum, forensic and anthropological studies, gender estimation, logistic regression

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Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

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Authors: Josephine Hai, Jie Jiang, Karen M. Lyons

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Of the musculoskeletal tissues, tendon is least understood in terms of biological development. The current study examines Cysteine-rich angiogenic inducer 61, or CCN1, a member of the CCN family of secreted matricellular proteins that regulate cell behavior via intercellular signaling. Though CCN1 is notable in limiting fibrosis by inducing senescence in fibroblasts, little is known about its role in normal fibrous tissue, where it may be essential to the development of ECM-rich structures like tendons. We found that CCN1 knockout mice (using limb-specific Prx1-Cre) exhibited clubfoot and waddling gaits, a unique phenotype not described in any other mutant to date. Histological analysis showed that the Achilles and patellar tendons, where we previously found high CCN1 expression in adult reporter mice, were thicker and denser in the Prx1-Cre knockouts than in their wildtype littermates. We then hypothesized that CCN1 is required directly in tendon progenitor cells for normal tendon development and generated tendon-specific CCN1 knockout mice using Scx-Cre. We observed similar Achilles/patellar tendon morphology among the Scx-Cre and Prx1-Cre mutants, indicating that the phenotype is a direct result of CCN1’s loss in tendon. To further study phenotype onset and progression, we will histologically characterize these tendons across different developmental time-points. We will also perform RNA-seq and qPCR to analyze tenocyte gene expression and expect fibrotic marker upregulation in the Scx-Cre mutants if CCN1 is required to maintain a normal tendon phenotype. Thus, our study aims to elucidate the molecular mechanisms underlying tendon formation and maintenance. Understanding tendons at the most basic level invites novel approaches to tendon repair.

Keywords: development, matricellular, musculoskeletal, tendon

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Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

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Authors: Ajmal Hussain

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In Indian music parlance, Rasa denotes a distinct aesthetic experience that builds up in the mind of the listeners while listening to a piece of Indian classical music. The distinction of the experience is rooted in the concept that it gives rise to an enhanced awareness about the Self or God and creates a mental state detached from mundane issues of everyday life. The theory of Rasa was initially proposed in the context of theatre but became a part of Indian musicological discourse roughly two thousand years ago, however, to this day, it remains shrouded in mystery due to its religious associations and connotations. This paper attempts to demystify the theory of Rasa in the light of available scientific knowledge fund particularly in Brain and Mind sciences. The paper initially describes the religious context of the theory of Rasa and then discusses its classical formulations by Bharata and Abhinavagupta including the steps and stages laid down by the latter to explain the creation of musical experience. The classical formulations are then interpreted with reference to the scientific knowledge fund about the human mind and mechanics of perception. The study uses the model of human mind as proposed by Portuguese-American neuroscientist Antonio Damasio in his theory ‘A Nesting Principle’. On the basis of the findings by Damasio, the paper interprets the experience of Rasa from a scientific perspective and clarifies the sequence of steps and stages involved in the making of musical experience. The study concludes that although the classical formulations of Rasa identify key aspects of musical experience, the association of Rasa with religion is misleading. The association with religion does not depend upon musical stimulus but the intellectual orientation of the listener. It further establishes that the function of Rasa is more profound as, from an evolutionary perspective, it can be seen as a catalyst for higher consciousness.

Keywords: aesthetic, consciousness, music, Rasa

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Authors: I. M. Fakai, A. Abdulhamid, I. Sani, F. Bello, E. O. Olusesi

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The phytochemical screening and hepatotoxic effect of Datura metel aqueous seeds extract in Albino Wistar rats were evaluated. Phytochemicals were screened using standard methods. The enzymes activity and liver function indices were also determined using standard methods of analysis. The phytochemicals screening revealed the presence of alkaloid, tannin, glycoside and flavonoid. The organ-body weight decreased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The activity of alkaline phosphatase decreased significantly (P<0.05) in the liver and increased significantly in the serum at all the doses of the extract treated groups compared to the control. The activity of serum alanine transaminase increased significantly (P<0.05) while there is no significant difference (P>0.05) in the activity liver alanine transaminase at all the doses of the extract treated groups compared to the control. The result also revealed significant increase (P<0.05) in the aspartate transaminase activity in both liver and serum at all doses of the extract treated groups compared to the control. Serum total protein, albumin, globulin, and total bilirubin concentration decreased significantly (P<0.05), while direct bilirubin concentration increased significantly (P<0.05) at all the doses of the extract treated groups compared to the control. The present study therefore revealed that, the present of some phytochemicals in the plant extract attributed the plant to its hepatotoxic effects as revealed in the alteration of marker enzymes and some liver function indices analyzed.

Keywords: datura metel, transaminases, hepatotoxic effect, phytochemicals, rats

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Authors: Heba Esaily, Rawhia Eledl, Daila Aboelela, Rasha Noreldin

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Objective: Assess serum level of Transforming growth factor beta 2 (TGF-β2) and Matrilin-3 (MATN3) SNP6 polymorphism in osteoarthritic patients Background: Osteoarthritis (OA) is a musculoskeletal disease characterized by pain and joint stiffness. TGF-β 2 is involved in chondrogenesis and osteogenesis, It has found that MATN3 gene and protein expression was correlated with the extent of tissue damage in OA. Findings suggest that regulation of MATN3 expression is essential for maintenance of the cartilage extracellular matrix microenvironment Subjects and Methods: 72 cases of primary OA (56 with knee OA and 16 with generalized OA were compared with that of 18 healthy controls. Radiographs were scored with the Kellgren-Lawrence scale. Serum TGF-β2 was measured by using (ELISA), levels of marker were correlated to radiographic grading of disease and MATN3 SNP6 polymorphism was determined by (PCR-RFLP). Results: MATN3 SNP6 polymorphism and serum level of TGF-β2 were higher in OA compared with controls. Genotype, NN and N allele frequency were higher in patients with OA compared with controls. NN genotype and N allele frequency were higher in knee osteoarthritis than generalized OA. Significant positive correlation between level of TGFβ2 and radiographic grading in group with knee OA, but no correlation between serum level of TGFβ2 and radiographic grading in generalized OA. Conclusion: MATN3 SNP6 polymorphism and TGF-β2 implicated in the pathogenesis of osteoarthritis. Association of N/N genotype with primary osteoarthritis emphasizes on the need for prospective study include larger sample size to confirm the results of the present study.

Keywords: Matrilin-3, transforming growth factor beta 2, primary osteoarthritis, knee osteoarthritis

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Authors: Sun fang, Zhang Wenxin

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This paper establishes an evaluation index system for spatio-temporal patterns of urbanization, with the county as research unit. We use the Entropy Weight method, coefficient variance, the Theil index and ESDA-GIS to analyze spatial patterns and evolutionary characteristics of New-Type Urbanization in the Central Plains Economic Region (CPER) between 2000 and 2011. Results show that economic benefit, non-agricultural employment level and level of market development are the most important factors influencing the level of New-Type Urbanization in the CPER; overall regional differences in New-Type Urbanization have declined while spatial correlations have increased from 2000 to 2011. The overall spatial pattern has changed little, however; differences between the western and eastern areas of the CPER are clear, and the pattern of a strong west and weak east did not change significantly over the study period. Areas with high levels of New-Type Urbanization were mostly distributed along the Beijing-Guangzhou and LongHai Railways on both sides, a new influx of urbanization was tightly clustered around ZhengZhou in the Central Henan Urban Agglomeration, but this trend was found to be weakening slightly. The level of New-Type Urbanization in municipal districts was found to be much higher than it was in the county generally. Provincial borders experienced a lower rate of growth and a lower level of New-Type Urbanization than did any other areas, consistently forming clusters of cold spots and sub-cold spots. The analysis confirms that historical development, location, and diffusion effects of urban agglomeration are the main drivers of changes in New-Type Urbanization patterns in CPER.

Keywords: new-type urbanization, spatial pattern, central plains economic region, spatial evolution

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Dipali Dhawan

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Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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Authors: Taleb L., Benarbia M., Boutira F. M., Allam H., Boukerche A.

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Introduction and purpose of the study: Meningiomas are the most common non-glial intracranial tumors in adults, accounting for approximately 30% of all central nervous system tumors. The aim of our study is to determine the epidemiological, clinical, therapeutic, and evolutionary characteristics of a cohort of patients with intracranial meningioma treated with radiotherapy at the Emir Abdelkader Cancer Center in Oran. Material and methods: This is a retrospective study of 44 patients during the period from 2014 to 2020. The overall survival and relapse-free survival curves were calculated using the Kaplan-Meier method. Results and statistical analysis: The median age of the patients was 49 years [21-76 years] with a clear female predominance (sex ratio=2.4). The average diagnostic delay was seven months [2 to 24 months], the circumstances of the discovery of which were dominated by headaches in 54.5% of cases (n=24), visual disturbances in 40.9% (n=18), and motor disorders in 15.9% (n=7). The seat of the tumor was essentially at the level of the base of the skull in 52.3% of patients (n=23), including 29.5% (n=13) at the level of the cavernous sinus, 27.3% (n=12) at the parasagittal level and 20.5% (n=9) at the convexity. The diagnosis was confirmed surgically in 36 patients (81.8%) whose anatomopathological study returned in favor of grades I, II, and III in respectively 40.9%, 29.5%, and 11.4% of the cases. Radiotherapy was indicated postoperatively in 45.5% of patients (n=20), exclusive in 27.3% (n=12) and after tumor recurrence in 27.3% of cases (n=18). The irradiation doses delivered were as follows: 50 Gy (20.5%), 54 Gy (65.9%), and 60 Gy (13.6%). With a median follow-up of 69 months, the probabilities of relapse-free survival and overall survival at three years are 93.2% and 95.4%, respectively, whereas they are 71.2% and 80.7% at five years. Conclusion: Meningiomas are common primary brain tumors. Most often benign but can also progress aggressively. Their treatment is essentially surgical, but radiotherapy retains its place in specific situations, allowing good tumor control and overall survival.

Keywords: diagnosis, meningioma, surgery, radiotherapy, survival

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Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

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Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

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Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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Authors: Sekena H. Abd El-Aziem, Heba A. M. Abd El-Kader, Sally S. Alam, Othman E. Othman

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Growth hormone (GH) is an anabolic hormone synthesized and secreted by the somatotroph cells of the anterior lobe of the pituitary gland in a circadian and pulsatile manner, the pattern of which plays an important role in postnatal longitudinal growth and development, tissue growth, lactation, reproduction as well as protein, lipid and carbohydrate metabolism. The aim of this study was to detect the genetic polymorphism of GH gene in five camel breeds reared in Egypt; Sudany, Somali, Mowaled, Maghrabi and Falahy, using PCR-RFLP technique. Also this work aimed to identify the single nucleotide polymorphism between different genotypes detected in these camel breeds. The amplified fragment of camel GH at 613-bp was digested with the restriction enzyme MspI and the result revealed the presence of three different genotypes; CC, CT and TT in tested breeds and significant differences were recorded in the genotype frequencies between these camel breeds. The result showed that the Maghrabi breed that is classified as a dual purpose camels had higher frequency for allele C (0.75) than those in the other tested four breeds. The sequence analysis declared the presence of a SNP (C→T) at position 264 in the amplified fragment which is responsible for the destruction of the restriction site C^CGG and consequently the appearance of two different alleles C and T. The nucleotide sequences of camel GH alleles T and C were submitted to nucleotide sequences database NCBI/Bankit/GenBank and have accession numbers: KP143517 and KP143518, respectively. It is concluded that only one SNP C→T was detected in GH gene among the five tested camel breeds reared in Egypt and this nucleotide substitution can be used as a marker for the genetic biodiversity between camel breeds reared in Egypt. Also, due to the possible association between allele C and higher growth rate, we can used it in MAS for camels and enter the camels possess this allele in breeding program as a way for enhancement of growth trait in camel breeds reared in Egypt.

Keywords: camel breeds in Egypt, GH, PCR-RFLP, SNPs

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Authors: Amin Abbasi, Fariborz Shekari, Seyed Bahman Mousavi

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Seed aging during storage is a complex biochemical and physiological processes that can lead to reduce seed germination. This phenomenon associated with increasing of total antioxidant activity during aging. To study the effects of hormones on seed aging, aged wheat seeds (control, 90 and 80% viabilities) were treated with GA3, Salicylic Acid, and paclobutrazol and antioxidant system were investigated as molecular biomarkers for seed vigor. The results showed that, seed priming treatment significantly affected germination percentage, normality seedling percentage, H2O2, MDA, CAT, APX, and GPX activates. Maximum germination percentage achieve in GA3 priming in control treatment. Germination percentage and normal seedling percentage increased in other GA3 priming treatment compared with other hormones. Also aging increased MDA, H2O2 content. MDA is considered sensitive marker commonly used for assessing membrane lipid peroxidation and H2O2result in toxicity to cellular membrane system and damages to plant cells. Amount of H2O2 and MDA declined in GA3 treatment. CAT, GPX and APX activities were reduced by increasing the aging time and at different levels of priming. The highest APX activity was observed in Salicylic Acid control treatment and the highest GPX and CAT activity was obtained in GA3 control treatment. The lowest MDA and H2O2 showed in GA3 control treatment, too. Hormone priming increased Antioxidant enzyme activity and decreased amount of reactive oxygen space and malondialdehyde (MDA) under aging treatment. Also, GA3 priming treatments have a significant effect on germination percentage and number of normal seedling. Generally aging seed, increase ROS and lipid peroxidation. Antioxidant enzymes activity of aged seeds increased after hormone priming.

Keywords: hormones priming, wheat, aging seed, antioxidant, lipid peroxidation

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Authors: Ali Kassem

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Background: In the last few years, factors such as insulin resistance (IR) and hepatic steatosis have been linked to progression of hepatic fibrosis.Patients with chronic liver disease, and cirrhosis in particular, are known to be prone to IR. However, chronic HCV (hepatitis C) infection may induce IR, regardless of the presence of liver cirrhosis. Our aims are to study insulin resistance (IR) assessed by HOMA-IR (Homeostatic Model Assessment Insulin Resistance) as a possible risk factor in disease progression in cirrhotic patients and to evaluate the role of IR in hepatic fibrosis progression. The correlations of HOMA-IR values to laboratory, virological and histopathological parameters of chronic HCV are also examined. Methods: The study included 50 people divided into 30 adult chronic hepatitis C patients diagnosed by PCR (polymerase chain reaction) within previous 6 months and 20 healthy controls. The functional and morphological status of the liver were evaluated by ultrasonography and laboratory investigations including liver function tests and by liver biopsy. Fasting blood glucose and fasting insulin levels were measured and body mass index and insulin resistance were calculated. Patients having HOMA-IR >2.5 were labeled as insulin resistant. Results: Chronic hepatitis C patients with IR showed significantly higher mean values of BMI (body mass index) and fasting insulin than those without IR (P < 0.000). Patients with IR were more likely to have steatosis (p = 0.006), higher necroinflammatory activity (p = 0.05). No significant differences were found between the two groups regarding hepatic fibrosis. Conclusion: HOMA-IR measurement could represent a novel marker to identify the cirrhotic patients at greater risk for the progression of liver disease. As IR is a potentially modifiable risk factor, these findings may have important prognostic and therapeutic implications. Assessment of IR by HOMA-IR and improving insulin sensitivity are recommended in patients with HCV and related chronic liver disease.

Keywords: hepatic fibrosis, hepatitis C virus infection, hepatic steatosis, insulin resistance

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Authors: Swati Kapoor, Rajeev Upreti, Monica Mahajan, Abhaya Indrayan, Dinesh Srivastava

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Enteric Fever is caused by gram negative bacilli Salmonella typhi and paratyphi. It is associated with high morbidity and mortality worldwide. Timely initiation of treatment is a crucial step for prevention of any complications. Cultures of body fluids are diagnostic, but not always conclusive or practically feasible in most centers. Moreover, the results of cultures delay the treatment initiation. Serological tests lack diagnostic value. The blood counts can offer a promising option in diagnosis. A retrospective study to find out the relevance of leucopenia and eosinopenia was conducted on 203 culture proven enteric fever patients and 159 culture proven non-enteric fever patients in a tertiary care hospital in New Delhi. The patient details were retrieved from the electronic medical records section of the hospital. Absolute eosinopenia was considered as absolute eosinophil count (AEC) of less than 40/mm³ (normal level: 40-400/mm³) using LH-750 Beckman Coulter Automated machine. Leucopoenia was defined as total leucocyte count (TLC) of less than 4 X 10⁹/l. Blood cultures were done using BacT/ALERT FA plus automated blood culture system before first antibiotic dose was given. Case and control groups were compared using Pearson Chi square test. It was observed that absolute eosinophil count (AEC) of 0-19/mm³ was a significant finding (p < 0.001) in enteric fever patients, whereas leucopenia was not a significant finding (p=0.096). Using Receiving Operating Characteristic (ROC) curves, it was observed that patients with both AEC < 14/mm³ and TCL < 8 x 10⁹/l had 95.6% chance of being diagnosed as enteric fever and only 4.4% chance of being diagnosed as non-enteric fever. This result was highly significant with p < 0.001. This is a very useful association of AEC and TLC found in enteric fever patients of this study which can be used for the early initiation of treatment in clinically suspected enteric fever patients.

Keywords: absolute eosinopenia, absolute eosinophil count, enteric fever, leucopenia, total leucocyte count

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Authors: N. V. Kazmiruk, Y. R. Nartsissov

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Phosphate activated glutaminase (GA, E.C. 3.5.1.2) plays a key role in glutamine/glutamate homeostasis in mammalian brain, catalyzing the hydrolytic deamidation of glutamine to glutamate and ammonium ions. GA is mainly localized in mitochondria, where it has the catalytically active form on the inner mitochondrial membrane (IMM) and the other soluble form, which is supposed to be dormant. At present time, the exact localization of the membrane glutaminase active site remains a controversial and an unresolved issue. The first hypothesis called c-side localization suggests that the catalytic site of GA faces the inter-membrane space and products of the deamidation reaction have immediate access to cytosolic metabolism. According to the alternative m-side localization hypothesis, GA orients to the matrix, making glutamate and ammonium available for the tricarboxylic acid cycle metabolism in mitochondria directly. In our study, we used a multi-compartment kinetic approach to simulate metabolism of glutamate and glutamine in the astrocytic cytosol and mitochondria. We used physiologically important ratio between the concentrations of glutamine inside the matrix of mitochondria [Glnₘᵢₜ] and glutamine in the cytosol [Glncyt] as a marker for precise functioning of the system. Since this ratio directly depends on the mitochondrial glutamine carrier (MGC) flow parameters, key observation was to investigate the dependence of the [Glnmit]/[Glncyt] ratio on the maximal velocity of MGC at different initial concentrations of mitochondrial glutamate. Another important task was to observe the similar dependence at different inhibition constants of the soluble GA. The simulation results confirmed the experimental c-side localization hypothesis, in which the glutaminase active site faces the outer surface of the IMM. Moreover, in the case of such localization of the enzyme, a 3-fold decrease in ammonium production was predicted.

Keywords: glutamate metabolism, glutaminase, kinetic approach, mitochondrial membrane, multi-compartment modeling

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